Apoptosis, or programmed cell death, is a naturally occurring process that has been strongly conserved during evolution to prevent uncontrolled cell proliferation. This form of cell suicide plays a critical role in ensuring the development and maintenance of multicellular organisms by eliminating superfluous or unwanted cells. Insufficient apoptosis, triggered by growth factors, extracellular matrix changes, CD40 ligand, viral gene products, neutral amino acids, zinc, estrogen, and androgens, can contribute to the development of cancer (Afford and Randhawa, Mol. Pathol., 2000, 53, 55-63).
Current treatments for cancer are centered on chemotherapeutic agents and radiation therapy. The goal of these two regimens is usually considered to be the killing of rapidly dividing cells by interfering with processes involved in the replication of cells. These treatments exploit the susceptibility of dividing cells to certain agents. Some of these methods include treatments designed to damage microtubule assembly during mitosis such as colchicine and paclitaxel (Kaufmann and Earnshaw, Experimental Cell Research, 2000, vol. 256, pp. 42-49). Other chemotherapeutic drugs that interfere with the replication of DNA such as doxorubicin and epirubucin (Buschini, et al., Mutagenesis, 2003, vol. 18, no. 1, pp. 25-36).
While these current therapies are targeted to cancerous cells, they have similar effects on otherwise healthy cells involved in the cell division process. There remains a need in the art for compounds and pharmaceutical compositions and methods useful for treatment, prevention and diagnosis of a variety of cancers.